Tetrahydrofolate synthetase (to be referred to as C1-THFS hereinafter) is an enzyme which synthesizes a tetrahydrofolic acid derivative that provides C1 group necessary for various metabolic reactions (Non-patent Reference 1; hereinafter, tetrahydrofolic acid is referred to as TF, and tetrahydrofolic acid derivative as TF derivative). Illustratively, TF derivatives give C1 group to the biosynthesis reactions of purine, thymidylic acid. histidine, pantothenic acid and the like. That is, TF and TF derivatives are deeply concerned in nucleic acid metabolism, amino acid metabolism and the like. Thus, TF and TF derivatives are found in tissues where cell division is vigorously carried out and essential for cell multiplication and growth.
C1-THFS is a tri-functional enzyme which has 3 types of functions. Illustratively, C1-THFS has the functions of 10-formyl-THF synthetase (EC 6.3.4.3), 5,10-methenyl-THF cyclohydrolase (EC 3.5.4.9) and 5,10-methylene-THF dehydrogenase (EC 1.5.1.5). By exerting these functions, C1-THFS accelerates synthesis of TF derivatives which are necessary for various metabolic reactions.
Analysis of C1-THFS has been carried out using human, mouse, yeast and the like eucaryote, Escherichia coli and the like procaryote and the like various organism species as the object (Non-patent References 2 to 5). Regarding yeast, the presence of a C1-THFS which functions in its cytoplasm and mitochondria is known. Also, regarding human, the presence of a C1-THFS which functions in the cytoplasm of its cells is known.
However, the presence of a C1-THFS which functions in the mitochondria of human cells is not known, and there is only one report of Non-patent Reference 19. In addition, a human C1-THFS gene whose expression is elevated in colon cancer tissue in comparison with normal colon tissue is not known, too.
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